Central and peripheral myeline sheaths contain a high molecular weight glycoprotein that is selectively localized in the inner portion of the sheaths adjacent to the axon. This glycoprotein, referred to as the myelin-associated glycoprotein (MAG), is specific for the nervous system and is present in greater amounts in the CNS than in the PNS. A major structural component of compact peripheral myelin (PO) is also glycosylated. Since membrane glycoproteins are known to be involved in recognition and cell-cell interactions, these myelin-related glycoproteins are being studied with regard to their likely roles in glia-axon interactions and myelin compaction. MAG undergoes a decrease in molecular size during development that correlates well with myelin maturation. The chemical and immunological properties of the mature and immature forms of MAG are being investigated. Since glycoproteins are well known to be cell-surface antigens and receptors for viruses, MAG may be involved in the putative autoimmune or viral aspects of multiple sclerosis or other demyelinating diseases. MAG is one of the earliest components to be lost in growing multiple sclerosis plaques, suggesting an important involvement in the pathogenesis of this disease.